Regional cardiac tissue treatment

ABSTRACT

A method for treating an occlusion in a coronary artery of a patient includes percutaneously advancing an occlusion treatment tool (such as an angioplasty balloon or stent delivery device) through the vasculature of the patient and into a coronary artery to a site of the occlusion. Following the treatment of the occlusion, a therapeutic agent is admitted into the first coronary artery. The therapeutic agent is selected to treat microvasculature obstructions at a target cardiac tissue site distal to the site of the occlusion.

I. CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation-in-part of commonly assignedInternational patent application Serial No. PCT/AU2005/000237 filed Feb.23, 2005 designating the United States and naming as inventors: DavidMartin Kaye, John Melmouth Power, Adam L. Bilney (all citizens ofAustralia) and Clifton A. Alferness (a citizen of the United States)which claims benefit of U.S. provisional application Ser. No. 60/612,846filed Sep. 24, 2004 and claims benefit of U.S. provisional applicationSer. No. 60/548,038 filed Feb. 26, 2004, which applications areincorporated herein by reference. Serial No. PCT/AU2005/000237 was filedwith the U.S. Patent and Trademark Office as a national stage filing onAug. 25, 2006 as Ser. No. PCT/US07/16369.

II. BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention pertains to methods and apparatus for treating tissue ofa patient's heart. More particularly, this invention pertains to methodsand apparatus for treating a region of heart tissue with therapeuticagents for treatment of microvascular obstructions. Also, the presentinvention pertains to treating an infarcted region of cardiac tissue.

2. Description of the Prior Art

The heart includes numerous coronary arteries for supplying oxygenatedblood to the tissue of the heart. Occasionally, one or more of thesecoronary arteries may become fully or partially occluded. Upon suchoccurrence, the region of heart tissue served by the occluded vessel isdeprived of oxygen.

If the occlusion occurs in a large vessel (e.g., a proximal portion ofthe left anterior descending artery, LAD), a large portion of the heart(e.g., the left side of the heart) is affected. If the occlusion occursin a smaller vessel (e.g., a distal portion of the LAD or a branch ofthe LAD), a smaller region of heart tissue is affected.

The occlusion may progress to such a degree that the tissue in theregion may become ischemic. Such ischemic tissue may revive after beingre-supplied with an adequate flow of oxygenated blood. If left untreatedand inadequately supplied with oxygenated blood, such tissue can becomenecrotic. Necrotic or infarcted tissue is a permanent injury to hearttissue. Such infarcted areas do not meaningfully participate in thepumping function of the heart. If the region of infarcted tissue islarge enough, the patient may develop heart failure or die.

A patient with a coronary artery occlusion may have symptoms (such aschest pain) upon exertion. Location of an occlusion can be determined byan angiogram procedure. In such a procedure, a radiopaque dye isinjected into the coronary arteries. The heart is inspected underfluoroscopy and the location of the occlusion is noted.

An occlusion can be treated in a number of different ways.Interventional treatments include surgery and percutaneous treatments.In surgery, a harvested blood vessel is attached to the occludedcoronary artery distal to the occlusion. Percutaneous proceduresinclude, among others, balloon angioplasty and stenting. In angioplasty,a balloon is placed in the artery in the region of the occlusion.Expansion of the balloon opens the occlusion. Stenting is similardiffering in that a stent (e.g., a metal cage) is left in place at thesite of the occlusion.

Intervention can greatly improve a patient's condition. However, asignificant number of patient's continue to experience symptomsconsistent with occlusion after such intervention. One cause of suchpersistent symptoms is believed to be microvascular obstruction. In suchpatients, the microvasculature of the heart (e.g., the arterioles andthe capillaries at which the oxygen-carbon dioxide exchange occurs) isoccluded with microscopic obstructions.

Microvascular obstruction is common in post-myocardial infarctionpatients. “In fully 25% of patients in whom arterial obstruction issuccessfully relieved, little to no additional myocardial perfusionresults. These patients . . . exhibit a substantial increase in overallmorbidity and mortality.” Alfayoumi, F., et al., “The No-ReflowPhenomenon: Epidemiology, Pathophysiology, and Therapeutic Approach”,Reviews in CV Medicine, Vol 6, No 2, p 72-83 (2005). The frequency ofmicrovascular obstruction is up to 44% in patients undergoing primaryinterventions for acute myocardial infarction. Marzilli M., et al.,“Primary Coronary Angioplasty in Acute Myocardial Infarction: ClinicalCorrelates of the ‘No Reflow’ Phenomenon”, International J. ofCardiology, Vol. 65 (Suppl. 1) pp. S23-S28 (1998). Assali, A R., et al.,“Intracoronary Adenosine Administered During Percutaneous Interventionin Acute Myocardial Infarction and Reduction in the Incidence of ‘NoReflow’ Phenomenon”, Catheter Cardiovasc Interv, Vol. 51, No. 1, pp.27-31 (2000).

Microvascular obstruction is associated with very serious negativeprognosis with profound clinical consequences including heart failure.Persistent microvascular obstruction is a more powerful predictor ofsurvival than infarct size and a high risk factor for late ventricularremodeling. Kramer, C. M., “The Prognostic Significance of MicrovascularObstruction after Myocardial Infarction as Defined by CardiovascularMagnetic Resonance”, European Heart Journal, Vol. 26, pp. 532-533(2005). “ . . . [T]he risk of subsequent major adverse events [is] asmuch as 10 times higher in the no-reflow population than in historicalcontrol patients.” Resnic, F S., et al., “No-Reflow is an IndependentPredictor of Death and Myocardial Infarction after PercutaneousIntervention”, American Heart J, Vol. 145, No. 1, pp. 42-46 (2003).

Currently, treatment options for microvascular obstruction are limitedand of generally inadequate effectiveness. Such treatments includesystemic infusion of vasodilators, anti-platelet, and anti-thrombinagents. These treatments have produced disappointing results. Treatmentoptions for ischemia are also limited. These include regional blood flowaugmentation and treatment for enhanced function. Such treatmentsinclude delivery of angiogenic agents to encourage new vessel growth andcell delivery to improve function.

More recently developed treatments for microvascular obstruction includeintracoronary injection of therapeutic agents to treat the microvascularocclusion. These agents include vasodilators (adenosine, verapamil,nitroprusside) and anti-platelet agents (IIb/IIIa). These treatmentsshow some promise. However, these treatments are supported by only verylimited studies. Also, such treatments have the potential for systemictoxicity.

It is an object of the present invention to provide a treatment formicrovascular obstruction in a region of a patient's heart and treatmentof regional myocardial ischemia.

III. SUMMARY OF THE INVENTION

According to a preferred embodiment of the present invention, a methodis disclosed for treating an occlusion in a coronary artery of apatient. The method includes percutaneously advancing an occlusiontreatment tool through the vasculature of the patient and into acoronary artery to a site of the occlusion. The tool may be any suitabletreatment such as an angioplasty balloon or stent delivery. Theocclusion is treated with the occlusion treatment tool. Following thetreatment of the occlusion, one or more therapeutic agents are admitted(either simultaneously or sequentially in the case of multiple agents)to the first coronary artery with the therapeutic agent. The therapeuticagent is selected to treat microvasculature obstructions at a targetcardiac tissue site distal to the site of the occlusion. Suitabletherapeutic agents include anti-thrombin agents, anti-platelet agents,anti-spasm agents and thrombolytic agents. At least a portion of a bloodflow is withdrawn from a coronary vein distal to the cardiac tissuesite. Additional embodiments include oxygenating the blood flowwithdrawn from the coronary vein and returning the oxygenated blood flowto the coronary artery. Also, a similar treatment for ischemia orinfarction is disclosed.

IV. BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic representation of a target region of cardiactissue to be treated and showing a major coronary artery and a smallerbranch coronary artery for supplying oxygenated blood to the region anda major coronary vein and a tributary coronary vein for directing bloodfrom the region back to the right atrium of the heart;

FIG. 2 is the view of FIG. 1 showing a perfusion catheter in the branchcoronary artery and showing a collection catheter in the tributarycoronary vein and showing a perfusion circuit;

FIG. 3 is the view of FIG. 1 showing a perfusion catheter in the branchcoronary artery and showing a collection catheter in the major coronaryvein and showing a perfusion circuit;

FIG. 4 is the view of FIG. 3 showing an alternative perfusion circuit;

FIG. 5 is a schematic showing of cardiac tissue receiving a supply ofoxygenated blood from a coronary artery with blood flow from the regionthrough a coronary vein and into a larger coronary vein such as thecoronary sinus and showing an occlusion at least partially blockingblood flow through the coronary artery;

FIG. 6 is the view of FIG. 5 showing an occlusion treatment tool passedinto the coronary artery through a delivery catheter;

FIG. 6A is the view of FIG. 6 showing an intermediate procedure forassessing regional perfusion including determining the presence ofmicrovascular obstructions in the cardiac tissue;

FIG. 6B is the view of FIG. 6 showing an alternative intermediateprocedure for assessing regional perfusion including determining thepresence of microvascular obstructions in the cardiac tissue;

FIG. 7 is the view of FIG. 6 following treatment of the occlusion andshowing a perfusion catheter admitted to the coronary artery through thedelivery catheter and showing a collection catheter in the coronaryvein;

FIG. 8 is the view of FIG. 7 showing the collection catheter in thecoronary sinus;

FIG. 9 is a view of a catheter for use in the present invention; and

FIG. 10 is an enlarged view of a distal end of the catheter of FIG. 9.

V. DESCRIPTION OF A PREFERRED EMBODIMENT

With reference now to the various drawing figures in which identicalelements are numbered identically throughout, a description of thepreferred embodiment of the present invention will now be described.

As will be more fully described, the present invention is mostpreferably used in concert with a percutaneous treatment for an occludedcoronary artery. In such use, the present invention may be used toprevent formation of micro obstructions in tissue distal to theobstruction or to treat preexisting micro obstructions in such tissue.Further, the present invention may be used as an independent therapy totreat or prevent micro obstructions of coronary tissue and to treatinfarcted tissue regions. Most of the following description describesthe invention in an embodiment for treatment of microvascularobstructions. However, the principles and techniques described are alsoapplicable to treating regional ischemia or infarction. Specifics ofsuch treatments are later described.

With initial reference to FIG. 1, a target cardiac tissue CT isschematically shown and labeled. The target cardiac tissue CT is tissueknown or suspected to contain micro-obstructions within the capillariesof the tissue or other impairment to flow within the capillaries.

Oxygenated blood flow to the target tissue CT is shown provided by abranch coronary artery CA₂ having a normal arterial blood flow rate ofAF₂. The branch coronary artery CA₂ receives blood from a major coronaryartery CA₁ having an arterial blood flow rate AF₁. It will beappreciated flow rate AF₁ is greater than flow rate AF₂. The remainderof the blood flow (i.e., AF₁ minus AF₂) is supplied by the majorcoronary artery CA₁ to other cardiac tissue (not shown).

By way of representative example, the major coronary artery CA₁ could bethe patient's main coronary artery or other major coronary artery (suchas the right coronary artery or the left anterior descending coronaryartery). The branch coronary artery CA₂ could be any artery branchingoff of the major coronary artery. Further, and by way of non-limitingexample, a left anterior descending artery may have a flow rate of about100 milliliters per minute (mL/min). A branch artery may have a flowrate of about 30 mL/min. It will be appreciated such rates vary frompatient to patient and, for any given patient, vary throughout the day.

Within the target tissue, oxygen from the blood flow of the branchcoronary artery CA₂ is exchanged with carbon dioxide through thecapillaries (not shown) in the target tissue CT. After such exchange,blood flow is returned to the heart by the blood first flowing through atributary coronary vein CV₂ into a major coronary vein CV₁ for ultimatedelivery to the right atrium (not shown) of the patient. The flow rateVF₂ in the tributary coronary vein CV₂ is less than the blood flow rateVF₁ in the major coronary vein CV₁.

The present invention delivers a therapeutic agent to the target tissueCT while substantially isolating the remainder of the cardiac tissuefrom such agent. This isolation permits delivery of the therapeuticagent only to the target tissue CT and avoids or minimizes delivery ofsuch agent to the remainder of the tissue of the patient's heart.Further, the present invention avoids delivery of such therapeutic agentsystemically to the patient. As a result, a higher dose of thetherapeutic agent may be applied to the target tissue than wouldotherwise be possible for safe delivery of such agent if deliveredsystemically or if delivered to the entire heart.

FIG. 2 illustrates a circuit 10 for isolated delivery of a therapeuticagent to the target cardiac tissue CT. A perfusion catheter 12 is shownpassed through the major coronary artery CA₁ and into the branchcoronary artery CA₂. A collection catheter 14 is shown passed throughthe major coronary vein CV₁ and into the tributary coronary vein CV₂.The collection catheter 14 has an inflatable balloon 16 at its distalend which may be inflated within the tributary coronary vein CV₂. As aresult, all blood flow VF₂ flows into the collection catheter 14.

Components for the circuit 10 (e.g., perfusion and collection catheters,oxygenators and pumps) are described in commonly assigned InternationalPatent Application Ser. No. PCT/AU2005/000237 filed Feb. 23, 2005 andpublished Sep. 9, 2005 as International Publication No. WO 2005/082440A1 (incorporated herein by reference).

In FIG. 2, a reservoir of a perfusate is shown at 20. The perfusate canbe any therapeutic agent selected for preventing formation ofmicrovascular obstructions or to treat existing micro obstructions. Byway of non-limiting example, suitable agents for use in the inventionare anti-thrombin agents, anti-platelet agents, anti-spasm agents andthrombolytic agents. Numerous ones of such agents already enjoy approvalby the U.S. Food and Drug Administration (FDA) for various indicationsand with established dosage guidelines.

Examples of such anti-thrombin agents include (names in parenthesis aretrade names): Bivalirudin (Angiomax), Hirudin (Refludan), low molecularweight heparin such as Dalteparin (Fragmin), low molecular weightheparin such as Enoxaparin (Lovenox), Heparin. Examples of suchanti-spasmodic agents include: Adenosine (Adenocard IV), Verapamil HCl,Nitro glycerin, Nitropusside, Lidocanine. Examples of such anti-plateletagents include abciximab (ReoPro) IIb/IIIa, Eptifibatide (Integrilin)IIb/IIIa, Tirofiban (Aggrastat) IIb/IIIa. Examples of such thrombolyticagents include Streptokinase, Anistreplase (Eminase), Alteplase or tPA(Activase), Reteplase (Retavase), Tecnecteplase (TNKase).

A delivery pump 22 draws the perfusate 20 through tubing 24 and deliversthe perfusate to the perfusate catheter 12. Tubing 26 connects theoutput of the collection pump 18 to an oxygenator 28. The oxygenator 28can be any commercially available unit for exchanging oxygen for carbondioxide contained within blood. In the embodiment of FIG. 2, theperfusate reservoir receives blood from the oxygenator 28 forrecirculation through the circuit 10.

As an alternative to the embodiment thus described, the pump 22 andreservoir 20 can be eliminated with blood delivered from the oxygenatordirectly to the perfusate catheter 12. Instead, perfusate could be addedto the tubing 10 through needle injection or IV-drip or the like from areservoir 20′ (shown in phantom lines) into a port 30.

With the embodiment of FIG. 2, a higher dose of the perfusate than couldotherwise be administered safely through systemic delivery or deliveryto the entire heart of the patient is administered directly and only tothe target tissue region CT.

In the embodiment of FIG. 3, the blood flow rate in the branch coronaryartery CA₂ is assumed to be approximate to the blood flow rate in thetributary coronary vein CV₂. In practice, it may not be possible toplace the collection catheter 14 in a small enough coronary vein havinga flow rate comparable to the flow rate in the coronary artery in whichthe perfusate catheter 12 resides. This is illustrated as an alternativecircuit 10′ in FIG. 3.

In FIG. 3, the perfusate catheter 12 is placed within the branchcoronary artery CA₂ as in the embodiment of FIG. 2. However, FIG. 3assumes that the collection catheter 14 cannot be safely or convenientlyplaced within a tributary coronary vein CV₂ having a flow ratecomparable to the flow rate of the branch coronary artery CA₂. Instead,the collection catheter 14 is placed within a larger coronary vein CV₁having a greater flow rate.

Since the collection catheter 14 collects all of the blood flow from themajor coronary vein CV₁, such blood flow cannot be re-circulated backinto the branch coronary artery CA₂. Accordingly, the blood collected inthe collection catheter 14 is pumped into a collection reservoir 32. Theblood within the reservoir 32 can be collected and later discarded. Itis generally recognized that blood amounts less than 250 milliliters maybe safely removed from a patient. Such blood flow loss is anticipated tobe small since it is anticipated that the delivery of perfusate by theperfusate catheter 12 will occur for only a short period of time (forexample five to ten minutes) for a therapeutic treatment.

In lieu of discarding the blood, it may be treated to remove or reducethe perfusate in the blood. So treated, the blood may be returned (withor without oxygenation) to catheter 12. Such treatments may includefiltering the blood, spinning the blood to collect and return the bloodas packed cells or treating the blood with serum/clotting factors orother cleansing treatments including dialysis.

Alternatively, a portion of the blood flow from the collection catheter14 (matching the flow rate in the branch coronary artery CA₂) can bereturned through an oxygenator 28 into the perfusate reservoir 20. InFIG. 3, this diverted flow is illustrated by the dotted line tube 26′.The flow is diverted by a flow control valve 34.

FIG. 4 illustrates a still further alternative circuit 10″. In FIG. 4,blood flow from the collection catheter 14 is passed through anoxygenator 28 into a catheter 36 for delivery to the major coronaryartery CA₁. While the blood delivered to the major artery contains theperfusate, it is diluted within the major artery. Further, suchperfusate is kept from circulating to other organs (such as the liver).

In FIG. 4, the perfusate reservoir can be an IV bag or syringe with theperfusate administered directly to the catheter 12 without a need forpump 22.

FIGS. 9 and 10 illustrate a catheter system for use in the embodiment ofFIG. 4. The catheter 36 includes a portion 36′ connected to the outputof the oxygenator of FIG. 4. At a couple 40, the perfusion catheter 12is received within the lumen of catheter 36. At the coupling 40, theperfusion reservoir 20 (a syringe injection in FIG. 9) admits perfusateto the catheter 12. Catheter 36 resides within the major coronary arteryCA₁. Catheter 12 extends from catheter 36 into the branch coronaryartery CA₂. The distal end of catheter 12 may be closed or open. Ineither event, catheter 12 preferably has a plurality of holes throughits side wall along a length L (e.g., five centimeters) for delivery ofthe perfusate into the branch coronary artery CA₂.

As mentioned earlier, the present invention is preferably used inconcert with a procedure for treating an obstruction in a coronaryartery. This procedure is illustrated schematically in FIGS. 5-8.

In FIG. 6, coronary artery CA is shown supplying blood to a region ofcardiac tissue CT. Blood flow from the tissue CT passes through acoronary vein CV and into a larger coronary vein CS (for example, thecoronary sinus) for ultimate delivery to the right atrium of the heart.The coronary artery CA contains an occlusion O at least partiallyblocking blood flow to the tissue region CT.

FIG. 6 shows a delivery catheter 40 passed into the coronary artery CAto a site proximal to the obstruction O. An obstruction treatment tool42 is passed through the catheter 40 with the tool 42 positioned totreat the obstruction O. The tool 42 and treatment method for treatingthe obstruction may be any tool or treatment known in the prior art.Such tools include, by way of non-limiting example, expandable balloonsfor angioplasty procedures, stent delivery catheters for delivering astent to the location of the obstruction or atherectomy devices forbreaking up and removing an obstruction or localized delivery of agentsto dissolve the obstruction.

Following treatment, the obstruction is reduced in size or eliminated asillustrated by the reduced occlusion RO in FIG. 7. After such treatment,the guide catheter 40 may then be used to guide the perfusion catheter12 into the coronary artery CA as illustrated in FIG. 7.

In FIG. 7, the collection catheter 14 is placed within the coronary veinCV and occludes the vein with the balloon 16 to collect all of the bloodflow from the coronary vein. Incomplete occlusion (e.g., use of acollection catheter 14 without balloon 16) is acceptable as long as theamount of therapeutic agent in the remainder flow (i.e., total flow invein CV less the diverted flow to catheter 14) remains within clinicallyacceptable levels for systemic delivery.

In FIG. 7, the circuit for the delivery of the perfusate to theperfusion catheter 12 and the collection of the blood from the coronaryvein will be the same as disclosed and described with reference to FIG.2. In the event the collection catheter 14 cannot be placed within avein CV having a blood flow comparable to that of the blood flow in thecoronary artery CA, the collection catheter 14 can be placed in a largercoronary vein (such as the coronary sinus CS) as illustrated in FIG. 8.The balloon 16 occludes the coronary sinus CS to collect the entireblood flow of the coronary sinus CS which will include the blood flowfrom the target region CT. As described in reference to FIG. 7, partialocclusion of the coronary sinus CS is acceptable as long as the amountof therapeutic agent in the non-diverted flow is deemed safe forsystemic delivery.

The complete circuit for the treatment of FIG. 8 may be such as thatillustrated and described with reference to FIG. 3. The circuitry ofFIG. 4 can used if it is desired to admit the therapeutic agent to abranch artery of the originally occluded artery or if desired to admitthe therapeutic agent in a main artery of which the occluded artery is abranch.

Throughout the above, different catheters or other tools have beenshown, described and separately numbered for performing certainfunctions. For example, tools 50, 52 and 12 are separately shown anddescribed. It will be appreciated these functions can be performed witha single catheter avoiding the need for multiple catheter replacements.

A microvascular obstruction treatment as described can be used in anypercutaneous occlusion treatment as a precaution against known orsuspected microvascular obstructions in tissue distal to the occlusion.More preferably, the likelihood of such microvascular obstructions isfirst assessed before applying the microvascular obstruction treatment.

FIGS. 6A and 6B illustrate intermediate assessment techniques. In FIG.6A, a flow rate measurement tool 50 is passed through the deliverycatheter 40 after treatment of the occlusion as described with referenceto FIG. 6. The characteristics of the measured flow rate in the coronaryartery indicate the likelihood of microvascular obstructions in thecardiac tissue CT. For example, a low- or no-flow condition followingtreatment of the occlusion O indicates the presence of suchmicrovascular obstructions. In FIG. 6B, the assessment tool is apressure sensor 52 distal to an occluding balloon 54. Pressureparameters (such as absolute pressure or pressure waveform) indicate thelikelihood of microvascular obstructions in the cardiac tissue CT.Assessment of microvascular obstructions through such techniques isdescribed in Lemos, et al., “New Tools for Assessing MicrovascularObstruction in Patients with ST Elevation Myocardial Infarction”, Heart,Vol. 90, pp. 119-120 (2004).

The assessment procedures may also be performed throughout the admissionof the therapeutic agent to the artery. For example, if a treatmentprocedure is planned to last 10 minutes, it may be discontinued early inthe event an assessment procedure indicates faster effective treatmenthas occurred.

While the foregoing invention has been described with reference toplacing catheters in a single coronary artery, multiple coronaryarteries can be treated with delivery catheters and where the blood flowis collected in one or more collection catheters (e.g., delivery to theright coronary artery and the left anterior descending artery with asingle collection through the coronary sinus).

With the present invention, an occluded artery is treated to correct theocclusion. The microvascular obstruction therapy of the presentinvention is then applied. Preferably, the therapy is appliedimmediately after the occlusion treatment while the patient is still inthe catheter lab and the guide catheter 40 is in place. The perfusioncircuit 10, 10′ or 10″ can operate for a time (e.g., 15 minutes at adelivery rate of 50-100 mL/min., by way of non-limiting example) to morethoroughly treat the patient and reduce risks otherwise associated withmicrovascular obstruction.

The present invention is also useful for treating infarcted cardiactissue. In treatment of an infarcted tissue region, the perfusioncatheter is placed in a coronary artery perfusing substantially only theinfarcted tissue region. The collection catheter may be placed in anycoronary vein such as the coronary sinus, distal to the infarctedregion. Treatment (such as oxygenation) and return of the collectedblood can be according to any of the embodiments described above. Theperfusate is a therapeutic agent selected for treatment of infarctedtissue regions. Such agents include angiogenetic agents to promote newvessel growth, agents to promote new myocardial cell growth, agents toprevent fibrosis, and other agents to minimize the infarct size and ordegree of dysfunctional. Such agents could be delivered in the form ofproteins, gene based agents or cells, such as but not limited to stemcells. One of ordinary skill in the art will readily recognize variousagents within these categories.

With the foregoing detailed description of the present invention, it hasbeen shown how the objects of the invention have been attained in apreferred manner. Modifications and equivalents of disclosed conceptssuch as those which might readily occur to one skilled in the art areintended to be included in the scope of the claims which are appendedhereto. For example, the present invention can be applied to organsother than the heart to treat a region of the organ.

1. A method for treating an occlusion in a first coronary artery of apatient comprising: advancing an occlusion treatment tool through thevasculature of the patient and into the first coronary artery to acoronary artery site of the occlusion; treating the occlusion with theocclusion treatment tool; treating microvasculature obstructions at atarget cardiac tissue site distal to the coronary artery site of theocclusion, including admitting at least one therapeutic agent to thefirst coronary artery with the therapeutic agent selected to treatmicrovasculature obstructions; withdrawing at least a portion of a bloodflow from a coronary vein distal to the cardiac tissue site.
 2. A methodaccording to claim 1 comprising oxygenating the blood flow withdrawnfrom the coronary vein.
 3. A method according to claim 2 comprisingadmitting the oxygenated blood flow to the first coronary artery.
 4. Amethod according to claim 2 comprising admitting at least a portion ofthe oxygenated blood flow to a second coronary artery of which the firstcoronary artery is a branch.
 5. A method according to claim 1 comprisingdiscarding the blood flow withdrawn from the coronary vein.
 6. A methodaccording to claim 1 comprising: diverting a portion of the blood flowwithdrawn from the coronary vein; oxygenating the diverted portion;admitting the diverted and oxygenated blood flow to the first coronaryartery.
 7. A method according to claim 1 wherein, prior to the admittingof the therapeutic agent, the target cardiac tissue is assessed forlikelihood of containing microvascular occlusions.
 8. A method oftreating microvasculature obstructions in a target cardiac tissue regionof a patient's heart, said method comprising: placing a perfusioncatheter into a first coronary artery, the perfusion catheter permittingblood flow to the target cardiac tissue region during treatment of thetarget cardiac tissue region; treating microvasculature obstructions atthe target cardiac tissue, including admitting at least one therapeuticagent to the first coronary artery with the therapeutic agent selectedto treat microvascular obstructions; systemically isolating thetherapeutic agent by withdrawing at least a portion of a blood flow froma coronary vein distal to the target cardiac tissue region.
 9. A methodaccording to claim 8 comprising oxygenating the blood flow withdrawnfrom the coronary vein.
 10. A method according to claim 9 comprisingadmitting the oxygenated blood flow to the first coronary artery.
 11. Amethod according to claim 9 comprising admitting at least a portion ofthe oxygenated blood flow to a second coronary artery of which the firstcoronary artery is a branch.
 12. A method according to claim 8comprising discarding the blood flow withdrawn from the coronary vein.13. A method according to claim 8 comprising: diverting a portion of theblood flow withdrawn from the coronary vein; oxygenating the divertedportion; admitting the diverted and oxygenated blood flow to the firstcoronary artery.
 14. A method according to claim 8 wherein, prior to theadmitting of the therapeutic agent, the target cardiac tissue isassessed for likelihood of containing microvascular occlusions.
 15. Amethod of treating microvascular obstructions in a region of cardiactissue of a patient comprising: identifying a coronary artery of thepatient; placing a perfusion catheter into the identified coronaryartery such that the perfusion catheter permits blood flow through theregion of cardiac tissue during treatment; treating microvascularobstructions in the region by admitting at least one therapeutic agentto the identified coronary artery through the perfusion catheter withthe therapeutic agent selected to treat microvascular obstructions;systemically isolating the therapeutic agent by withdrawing at least aportion of a blood flow from a coronary vein distal to the region ofcardiac tissue.
 16. A method according to claim 15 comprisingoxygenating the blood flow withdrawn from the coronary vein.
 17. Amethod according to claim 16 comprising admitting the oxygenated bloodflow to the identified coronary artery.
 18. A method according to claim16, wherein the identified coronary artery is a first coronary artery,the method further comprising admitting at least a portion of theoxygenated blood flow to a second coronary artery of which the firstcoronary artery is a branch.
 19. A method according to claim 15comprising discarding the blood flow withdrawn from the coronary vein.20. A method according to claim 15 comprising: diverting a portion ofthe blood flow withdrawn from the coronary vein; oxygenating thediverted portion; admitting the diverted and oxygenated blood flow tothe identified coronary artery.